Good morning, and welcome to Axsome Therapeutics conference call. At this time, all participants are in a listen-only mode. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. With that, I would now like to turn the conference over to your host, Mark Jacobson, Chief Operating Officer at Axsome Therapeutics. Mark, please go ahead. Thank you, operator. Good morning, and thank you all for joining us on today's conference call. This morning we issued a press release announcing the approval of Auvelity for the treatment of major depressive disorder. The release crossed the wire a short time ago and is available on our website at axsome.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our investigational agents, our clinical and non-clinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development plans, commercial plans, and possible intended use of cash and investments. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today from the Axsome team are Dr. Herriot Tabuteau, Chief Executive Officer, Nick Pizzie, Chief Financial Officer, and Lori Englebert, Executive Vice President of Commercial and Business Development. Also joining us on the call today is one of the leading experts on major depressive disorder, Dr. Dan Iosifescu, Professor of Psychiatry at NYU Grossman School of Medicine. Herriot Tabuteau will first make some opening remarks. Dr. Iosifescu will provide an overview of major depressive disorder, and he will then discuss the clinical trial results and clinical profile of Auvelity. Following Dr. Iosifescu, Lori will provide an overview of our commercial plans. We will then open the line for questions, and questions will be taken in the order they are received. With that, I am pleased to turn the call over to Herriot Tabuteau. Thank you, Mark. Good morning, everyone. This morning we announced that the FDA has approved Auvelity for the treatment of Major Depressive Disorder, or MDD, in adults. The Axsome team is extremely pleased to deliver this breakthrough therapy designated new treatment to the millions of patients living with depression. This approval comes at a time when it is most needed, given the recent sharp increase in depression prevalence. Auvelity is the first and only oral NMDA receptor antagonist and the first and only oral antidepressant approved by the FDA as rapid acting for MDD. We are proud to be the company to make available to patients and their physicians the first new oral mechanism of action approved for MDD in over 60 years. This achievement is the culmination of the tremendous and focused research and development activities conducted by the Axsome team and our collaborators. Auvelity is protected by a robust patent estate extending out to at least 2037-2040. Our commercial team is ready, and the launch of Auvelity is planned for early Q4. The approval of Auvelity reflects Axsome's commitment to developing life-changing medicines for people living with serious central nervous system disorders. This commitment is further reflected by our broad neuroscience portfolio, which now includes five commercial or late-stage product candidates in clinical programs in eight different indications. Our commercial portfolio now consists of Auvelity for MDD and Sunosi for EDS in narcolepsy and obstructive sleep apnea. Our AXS-07 candidate for migraine is NDA stage. These agents are followed by our two phase III stage product candidates, AXS-12 for narcolepsy and AXS-14 for fibromyalgia, both of which have potential NDA filings in 2023. Lastly, we have important follow-on indications, including Alzheimer's disease agitation and ADHD, which are in or about to enter phase III trials. Overall, our industry-leading portfolio targets disorders experienced by more than 100 million patients in the U.S. alone. Auvelity was developed using Axsome's innovative and efficient approach to clinical development. This approach allowed us to initiate a phase II trial on MDD, obtain FDA breakthrough therapy designation, complete our efficacy and safety studies, and file the NDA with priority review in less than three years. We are pleased with the label for Auvelity, some of the key features of which are highlighted here. These include its novel oral NMDA receptor antagonist and sigma-1 receptor agonist mechanism of action. A broad indication to treat MDD in adults. Its rapid and durable efficacy with demonstrated improvement starting at week one that is maintained and increased through the end of treatment. Auvelity was also found to be safe and well-tolerated, with no psychotomimetic effects and no weight gain. The Auvelity label contains the boxed warning of increased risk of suicidal thoughts and behaviors in pediatric and young adult patients required for all approved antidepressants. Auvelity is not approved for use in pediatric patients. With that, it is my honor to introduce Dr. Dan Iosifescu, Professor of Psychiatry at NYU Grossman School of Medicine. Dr. Iosifescu is a leader in the field and a recognized expert in depression treatment. Dr. Iosifescu will present an overview of MDD and the phase three results and clinical profile of Auvelity. Thank you, Herriot Tabuteau. It is a real pleasure to provide this overview of major depressive disorder and to discuss the results from one of the registration trials of this new and exciting novel treatment. My name is Dan Iosifescu, and I'm a professor of psychiatry at the NYU Grossman School of Medicine. I'm also the director of the Clinical Research Division at the Nathan Kline Institute for Psychiatric Research. Next slide. I will start by providing a brief overview of major depressive disorder or MDD. It is important to highlight that MDD is a serious, chronic, disabling, and even life-threatening condition with very high rates of morbidity and mortality. The morbidity seen in patients with MDD includes profound distress, inability to work, and impaired social functioning. MDD is ranked by the World Health Organization as the single largest contributor to global disability. In fact, 7.5% of all years lost lived with disability in 2015 were related to MDD. This is because the condition starts when people are very young and affects a very large proportion of the population. The most severe feature of MDD is suicide, which can be attempted or successful. It is important to point out that the increased mortality is seen even in patients with MDD who do not commit suicide. In the average patient with MDD, the condition results in a median of 10 years of life lost because of the condition. As it concerns the mechanism underlying the disease, a growing body of evidence from various areas of research have implicated the glutamatergic system in the pathology of depression. Of note, the glutamatergic system is the most significant excitatory neurotransmitter in the brain. Next slide. MDD at baseline levels has been considered a very prevalent condition. However, this already high prevalence seems to have increased dramatically since the start of the COVID-19 pandemic. We used to refer to the fact that the average yearly prevalence of MDD was roughly about 10% per year. As shown on this slide, this prevalence rate has jumped to about 28% in 2020 and climbed even higher to about 33% in 2021. This translates to roughly a threefold increase in the prevalence of MDD since the start of the pandemic. The increase is thought to be related not only to the stress and social isolation provoked by the pandemic, but also to the neuroinflammatory factors associated with the actual infection. Suffice it to say that depression is a major public health concern that has recently increased in magnitude, resulting in a massive amount of pathology that requires our care. Next slide. Unfortunately, the treatments that we currently have have significant limitations. Chief among them are inadequate response and delayed onset of action. Inadequate response to currently available antidepressants is common and is seen in a large proportion of patients treated with these agents. The problem of inadequate response is compounded by the fact that current antidepressants are associated with a prolonged time to clinically meaningful response. It can take between six-eight weeks or even longer to truly discern if a patient will improve or not with a current antidepressant treatment. The result of the delayed onset of action with current treatments is greater patient suffering, increased risk, and greater expense. This is a burden that affects not only patients, but also their immediate social networks and ultimately the society at large. Very importantly, all currently approved oral agents for major depressive disorder work primarily through monoaminergic mechanisms. This is a very important point to consider, as it may explain the high rates of inadequate response with current treatments for major depressive disorder. Next slide. Shown here is a timeline of the approval of antidepressants and their respective mechanisms of action. The first antidepressants were the monoamine oxidase inhibitors and the tricyclics, which were initially discovered in the 1950s and 1960s. Over the next six decades, there were important antidepressants that were discovered and approved. However, all those agents work by modulating the monoaminergic neurotransmitter and receptors. For example, serotonin, norepinephrine, dopamine or a combination thereof. We knew that other brain pathways, such as the glutamatergic system, are very relevant to the pathology of depression. Until recently, clinicians did not have agents to adequately address these other potential pathways and use for treatment. That changed in 2019 with the approval of intranasal esketamine, SPRAVATO, for the treatment of depression. This was a significant milestone for the treatment of depression because the NMDA ionotropic glutamate receptor is the target of this treatment. A complete paradigm shift from the monoaminergic targeting of all the prior antidepressants. However, SPRAVATO has its limitations. It requires an in-office administration since it would be unsafe for a patient to self-administer the agent at home. It is also a controlled substance, and it is associated with significant dissociative effects. This really leaves a very significant unmet need to have a glutamatergic modulating drug that would be available as an oral pill and could be taken safely by patients at home. With the approval of Auvelity, patients and clinicians now have that oral glutamatergic modulating treatment. Auvelity is a proprietary oral NMDA receptor antagonist consisting of dextromethorphan and bupropion. The dextromethorphan is an antagonist of the NMDA ionotropic glutamate receptor and also a sigma one receptor agonist. The two mechanisms modulate glutamate transmission. The bupropion component is an aminoketone and a cytochrome P450 2D6 inhibitor which serves to increase the plasma level of dextromethorphan. Auvelity therefore uses the first new oral mechanism of action approved for depression in over 60 years. Next slide. I will now review the results of a large phase three registration trial of Auvelity and discuss its clinical profile. Next slide. Shown on this slide are the key efficacy results from the phase III trial of Auvelity in MDD, which was recently published in The Journal of Clinical Psychiatry. This was a randomized, double-blind, placebo-controlled trial in patients with MDD who were treated with either Auvelity or placebo twice daily for six weeks. The primary endpoint was the change from baseline in the total depression severity measured by the Montgomery-Åsberg Depression Rating Scale total score at week six. The key secondary endpoints designed to measure rapidity of onset were the change in MADRS at week one and at week two. I will draw your attention to the gold line, which represents the Auvelity group. As is shown in the graph, improvement for patients treated with Auvelity was significantly faster and greater in magnitude than in the placebo group. The improvement over placebo is statistically significant at all time points, starting with week one. The table on this slide summarizes the magnitude of the improvement. For the primary endpoint, which is the change in MADRS at week six, the Auvelity group has a near four-point advantage over placebo group. The improvement is not just statistically significant but very clinically significant. Just to give you some context, generally in depression trial, a separation of two points on the MADRS between the active component and placebo is considered to be a clinically significant difference. When looking at the key secondary endpoints at week one, Auvelity separates by more than two points from placebo, and that is again both statistically but also clinically meaningful. At week two, the placebo corrected difference with Auvelity is nearly 3.5 points. These results truly highlight the rapidity and the robustness of the clinical effect. Next slide. Shown on this slide are the percentages of patients achieving remission over time. Remission is the holy grail of antidepressant treatment. Achievement of remission is essentially a depression score in a patient that is at that time not significantly distinguishable from that of someone who does not have depression. It is defined on the MADRS scale as a score of 10 or less. As demonstrated on this graph, already at week two, the proportion of the patients achieving remission is higher in the group receiving Auvelity compared to the group receiving placebo. The separation between Auvelity and placebo in terms of remission rates continues and increases over time. The rate of remission with Auvelity is more than double the rate with placebo at week six. Again, this demonstrates a very robust clinical response. Next slide. In terms of safety in the trial, Auvelity was safe and well tolerated. The most common adverse events in the Auvelity group were dizziness, nausea, headache, somnolence, dry mouth, and sexual dysfunction. The rates for the individual adverse events were low, especially when compared with placebo. Finally, Auvelity was not associated with psychotomimetic effects, which are the dissociative symptoms, unpleasant, which are present with other glutamatergic medications like SPRAVATO. Auvelity was also not associated with weight gain, which is, an important negative side effect of other antidepressants. Next slide. In conclusion, Auvelity has demonstrated rapid, sustained, substantial, and statistically significant efficacy in major depressive disorder as compared to placebo. Auvelity demonstrated significant efficacy in major depressive disorder compared to placebo as early as week one after treatment. I really need to highlight that this is a really outstanding result, especially when compared with other antidepressants, which even when efficacious, take much longer. The achievement on remission rates, which, as I mentioned before, is really the holy grail of treatment in major depressive disorder, was significantly greater with Auvelity compared to placebo, starting as early as week two and then continuing for the entire duration of the study. The treatment difference for Auvelity compared to placebo was substantial at all time points. Auvelity was well tolerated. It was not associated with psychotomimetic effects or weight gain. On balance, due to its novel mechanism of action targeting both the glutamate system and the sigma-1 receptors, and due to its rapid and robust antidepressant efficacy that was demonstrated in this and other clinical trials, I truly believe that Auvelity is a welcome new and important treatment for patients with major depressive disorder. Thank you very much for your attention. Thank you, Dr. Iosifescu. We will now turn it over to Lori, who will discuss our commercial plans. Thank you, Herriot, and good morning, everyone. We are thrilled with the FDA approval for Auvelity. Auvelity is a potential game changer for the millions of patients living with major depressive disorder, and we are excited to finally bring this product to market. Launch preparations started well over a year ago. We are prepared and ready to execute. Before I discuss our commercial strategy and launch readiness, I'd first like to reiterate earlier commentary on the devastating prevalence trends and the potential opportunity Auvelity has to help those patients living with major depressive disorder. Major depressive disorder is highly prevalent. 21 million U.S. adults were diagnosed with MDD in 2020. As mentioned previously, studies estimate that depression prevalence may have risen last year to as high as 32.8% or 85 million U.S. adults. MDD is considered the number one leading cause of disability worldwide. Of those who are on therapy for the treatment of MDD, an overwhelming majority are not satisfied with their treatment experience. In 2022, Axsome partnered with Depression and Bipolar Support Alliance, DBSA, to quantify and better understand patient treatment experiences and expectations, along with treatment-related impacts on those taking antidepressants for major depressive disorder. This was a large study of 385 U.S. adults and a key finding highlighted that 78% of respondents were not satisfied with at least one of their current MDD treatments. Further insights also highlighted that despite being on therapy, 68% still reported symptoms. 52% reported having difficulty being productive as a result of depression, and 48% had trouble with side effects. Perhaps one of the most insightful results was that 82% believe that people with depression deserve better medications than what is currently available. Last year, in an effort to support the depression patient community, Axsome launched a patient-focused disease education campaign called Talk Depression. Talk Depression provides a platform for patient empowerment, support, and education for those impacted by major depressive disorder. The campaign was launched via digital and social media and has reached more than 11 million unique individuals. Results from survey questions asked on the website showed that 78% of all registrants were neutral to very disappointed with their depression treatment experience and 69% were planning to talk to their doctor about it. Results from the support survey and engagement with our Talk Depression campaign further highlight the high unmet need for better therapeutic options for patients. As I mentioned before, we are extremely excited to bring Auvelity to market. Our launch focus will be threefold. First, we will drive fast HCP adoption by strategically targeting, optimizing engagements using our proprietary digital-centric commercialization platform, and we will reach potential prescribers through a combination of personal and non-personal promotion. Second, we will empower patients by creating awareness of Auvelity through a targeted digital and social media campaign and by providing educational tools and support. Third, we will enable patient access by providing comprehensive and robust patient support services and by educating payers on the clinical benefit provided by Auvelity. As you heard in Herriot Tabuteau's review of the label, Auvelity is indicated for the treatment of major depressive disorder in adults and is a potential game changer for those living with MDD. Auvelity is the first mechanistically novel oral treatment for MDD in over 60 years and is the first and only NMDA receptor antagonist approved for the treatment of major depressive disorder. Auvelity demonstrated rapid, strong, and sustained efficacy in clinical trials and is the first and only oral antidepressant approved by FDA for rapid-acting efficacy starting at week one. Achievement of remission was demonstrated as early as week two, and Auvelity's magnitude of effect was statistically significant and clinically meaningful at week one and week six. Auvelity demonstrated sustained efficacy at week six across multiple scales and was generally well-tolerated and not associated with psychomimetic effects or weight gain. Auvelity's clinical profile has the potential to address many of the unmet needs associated with current treatments that were highlighted by Dr. Iosifescu. Our sales force launch strategy will focus on high-potential prescribers and utilize our digital centric commercialization or DCC platform. At launch, our 165-person field force will target 25,000 HCPs. Our 25,000 targets capture greater than 70% of the addressable market for Auvelity and are a mixture of psychiatrists and mental health-focused or MDD-specialized PCP. We estimate that our DCC-enabled field force will be able to achieve the same productivity as a traditional 250-rep field force. Axsome's DCC platform is a seamlessly integrated infrastructure of systems and tools supported by sophisticated AI and machine learning analytics. The intent behind the DCC platform is to enable efficient and effective engagements with both HCPs and patients. DCC allows for easy identification of the right targets, either HCPs or patients. Identifies the best way to engage face-to-face, remotely, digitally, socially, et cetera, and provides recommendations on the appropriate messaging. This approach is different than the broad stroke approaches traditionally used in pharma promotion and we believe creates both an efficient and effective engagement with our core audience by optimizing every touch point. We are in the process of finalizing the WAC price for Auvelity and expect to provide it in the coming weeks. Our intention is to price Auvelity in a way that ensures broad access for patients and that takes into account the value supported by the innovation Auvelity brings to patients with MDD. Antidepressant prescriptions largely flow through the commercial channel. Due to consolidation in recent years, five PBMs or payers manage 80% of MDD prescriptions. Through our highly experienced payer team, we have had permitted pre-approval payer discussions for well over a year now and intend to start working with payers to discuss the clinical profile and benefits of the product in the coming weeks. In order to ensure that patients have affordable access to Auvelity, along with ensuring physicians have an easy experience prescribing Auvelity, we have enabled a comprehensive suite of tools and services in our patient support program, Auvelity On My Side. Our patient support services will include sample programs, a savings program for eligible patients, and prior authorization support, among other tools. All programs will be available immediately upon launch and I look forward to informing you more about our patient support programs after launch. As previously mentioned, we are excited to bring this innovative new product to market and are prepared for a full commercial launch in early Q4. All new field force team members who were hired contingent upon approval will officially start in the coming weeks and will immediately commence training. I look forward to sharing more with you and reporting on our progress during the next earnings call. I will now turn the call back to Mark to lead the Q&A discussion. Thank you, Lori. With that, operator, may we please have our first question? Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. Confirmation tone will indicate your line is in the question queue. Thank you. Our first question comes from Charles Duncan with Cantor Fitzgerald. Your line is open. Hey, good morning, Herriot Tabuteau and team. You know, great day for patients and for Axsome. Congratulations. Thanks for taking our questions. My first question is for the Dr. Dan Iosifescu. I'm wondering, Dr. Dan Iosifescu, if you had to nail just one aspect of the clinical profile that you're most compelled with and may drive adoption, would it be speed of onset? Would it be response rate, magnitude of effect, or the remission effects that you've seen and highlighted? Then secondarily, do you think that the lack of being able to prescribe to pediatrics, at least initially, will impact that adoption rate? Hi, Charles. This is Herriot Tabuteau. Dr. Dan Iosifescu is not available for the Q&A portion, but let me take a crack at answering some of those questions. Yeah. What's he told you? Yeah. I think as you heard from his prepared remarks, and I think this reflects also our view, it's really the culmination of all of those aspects of the product, which is unique. It's rapid acting. It does have a very substantial magnitude of effect. You get remission quickly, and at high rates, and it's also very well tolerated. It's really the culmination of all of those factors which make it a unique approach. In addition to that, the fact that this is a totally new drug class, it hits the glutamatergic system, which no other drug currently does. The vast majority of patients, we know do not respond or have an adequate response to current, antidepressant drugs, which work, via other mechanisms of action. It's really a confluence of all of those attributes which make it compelling. With regards to the, lack of an indication in pediatric patients, that is normal. You know, all drugs that are launched initially are launched in the adult population. As you know, sponsors are required to develop the, or at least test the drug in pediatric patients. We do have a pediatric study plan in place. Okay. Very good. That's helpful. Hey, Charles, it's Lori. Yeah. I just wanted to jump in. We're very excited here, so everybody wants to talk. You know, we've done extensive market research with HCPs. You know, coupling with what Dr. Dan Iosifescu has conveyed to Ario and all of us. I just wanna give you kind of a quick overview of you know some of the comprehensive market research that we've done. You know, with you know symptom improvement happening at week one and then you know remission happening by week two, that to physicians, the combination of those two is incredibly differentiating in the marketplace right now. If you think about the high unmet need that remains in the market, you know, 2/3 of patients don't achieve remission. Physicians are now moving toward remission as the goal of treatment. You know, we're pretty excited about the clinical profile of the product. If I could ask you a follow-up, Lori or Ario. I guess I'm wondering, I know we'll have to wait for pricing, and it makes sense that you're nailing that down. But is there a trade-off between broad access and capturing the pharmacoeconomic value and differentiation of the product? Or do you think that you can achieve, you know, kind of both goals with premium pricing? Yeah. Yeah. I mean, we're not, you know, we will communicate price, you know, in the coming weeks or we hope to in the coming weeks. Thanks for the understanding on not having that finalized right now. I do believe it's possible to achieve both. I don't know what, you know, if your insinuation around premium pricing is meaning that we're gonna price extremely high. I think there is a broad understanding with payers that, you know, if you bring clinical benefit to the marketplace, you know, you have to figure out what that fine line is to make sure that you have broad access for patients. Because in our mind, you know, making sure that patients are able to get on the product is very important to us. Yeah. I didn't mean to insinuate extremely high pricing 'cause that's not what I anticipate you folks will do. Last question regarding robust IP. Herriot Tabuteau, you mentioned it earlier. Is there any one element of the IP for 37 versus 40 that you wanna point to? And do you think that any prescriber would, you know, right-minded prescriber would try to prescribe the two drugs, you know, as generics, or do you believe that you just it's clear to people that you won't be able to achieve the clinical profile of Auvelity with that strategy? With regards to that last question, Auvelity is a proprietary formulation, which is designed to provide a distinct pharmacokinetic profile. We've shown now in a dozen clinical trials, or a dozen or more clinical trials, which form the basis for the NDA, that this has resulted in a favorable efficacy profile in MDD and also a favorable safety and tolerability profile. As is documented now in our package insert, the complex pharmacokinetic interaction between the two components is actually nonlinear. What that means is that any attempt to get at that specific profile, you know, might be magnified with regards to any small changes in dose. We're very comfortable with the profile because we have demonstrated it in clinical trials, and that has resulted in the FDA approval of the product, which now tells clinicians exactly how to dose the product in a safe way and also in an efficacious way for patients. Very good. That ties into the robust IP, which you mentioned, which go out to at least 2037-2040. This has been a growing patent portfolio, which now consists of several different families of patents. You know, I would also add that that patent family continues to grow. Very good. Thanks for taking my questions, Herriot Tabuteau, and congratulations on this news. Good one. Thank you. Thank you. Our next questions come from the line of June Lee with Truist Securities. Your line is open. Hey, guys. Congrats on the approval, and thanks for taking our questions. This question was intended for the doctor from NYU, but, you know, since he's not here, at what point in the MDD treatment would you deploy Auvelity as a second line, third line, or later? Herriot and Lori, what is your expectation based on talking to some of the prescribers? And, also, you know, how much SPRAVATO is currently in use, and would that now switch over to Auvelity, or is that, is taking share from SPRAVATO not part of your strategy? I have a quick follow-up. I'll start, then maybe Lori can jump in. The Auvelity clinical development program looked at various lines of treatment. As you know, our clinical studies did look at dosing patients frontline, also second line and various lines of treatment, including patients with treatment-resistant depression. We've reported out those results, and what's nice is that you know you see a very consistent efficacy profile regardless of line of treatment. We do wanna point out that the label that has been approved is a broad one, so it's just for MDD. That encompasses any way that a clinician you know might want to treat a patient with MDD. Now, with regards to, you know, how it might be used in a real-world setting, as is well documented, roughly, you know, 2/3 of patients do not respond adequately to current treatments. And, MDD is also, you know, highly treated. Roughly 2/3 of patients are treated. So you do have, you know, a lot of patients out there who are in need, and, we're very happy to provide clinicians a new mechanism of action and a new way to treat those patients and the clinical data so that they can make their own decisions as to where they would wanna place it in terms of lines of treatment. Yeah, I couldn't agree more, Herriot Tabuteau. Thanks, thanks for that. Hi, June. Thanks for the questions. I'll just quickly touch on the SPRAVATO versus Auvelity. I, you know, Herriot Tabuteau said it best. SPRAVATO has a completely different indication than Auvelity has. We do not believe that we will be playing even remotely close to where SPRAVATO plays. Thank you for that. I have a couple of silly check-the-box kind of questions. Can you confirm that Auvelity has no REMS, no DEA scheduling, and that the rapid acting is on label, or is it that it's stat sig separating at week one, which they can interpret however they want? Yeah. We can confirm there is no REMS. We can confirm also that there is no DEA scheduling, so it's not scheduled. We can also confirm that it is on label, that it is rapid acting. As you know, the definition of rapid acting is that the drug works at one week. That is in our label in the clinical trial section that it starts working at one week. Great. Well, congrats on all the best on the launch. Thank you. Thank you. Thanks, June Lee. Thank you. Our next questions come from the line of Myles Minter with William Blair. Your line is now open. Yeah. Hey, guys. A huge congratulations to me. Milestone event for the company and for patients. Congrats. My question is just on the clinical data and the label. I just was going back and looking at the GEMINI top line data that the company presented versus what's actually in the label, and it does appear that at six weeks there's a slight difference between what you presented as a company and what the FDA has put in the prescribing label in terms of the MADRS delta versus placebo. Still looks clinically meaningful to me, but just wondering what reanalysis went on there and how they sort of came to that number versus the top line data number that you've been messaging out there. Thanks. Yeah, it's the same data. The difference is the LS mean versus an arithmetic mean. Okay. Just on the safety portion of the label. I mean, it does look like it's a combination of dextromethorphan and Wellbutrin labels here, with some issues that appear slightly elevated. I think I see some embryo fetal toxicity. I think that's in the bupropion label, but this has become a warning to precaution. Just wondering where a lot of these sort of elevated safety concerns have maybe come from. Is it due to the PK of this compound as described in the label, or is it more just the FDA taking a little bit more of a cautionary stance? Thanks. Myles, thanks for the question. We have not seen any elevated safety concerns. Now, the label with regards to things like embryo-fetal tox, which we did not see actually in our studies, but the label does reflect whether or not certain nonclinical studies have been conducted or completed, and some of those studies are actually postmarketing commitments. The label, the future label, will reflect the results of those studies. Okay. Thanks for the questions. I appreciate and congrats on the approval here. Thank you. Thank you. Our next questions come from the line of Marc Goodman with SVB. Your line is now open. Yes. Good morning, guys. Herriot, now that this is all done, maybe can you tell us what took so long? What was the FDA's issue? You know, we know that we have Relmada and Sage and your company all trying to come up with, you know, new mechanisms to the market, fast acting. I'm just curious if this whole fast onset was a question mark for the FDA of how to put it into the label, and versus an indication and stuff. Second question is what are your post-marketing commitments? You just started to mention that just in the previous one. Thanks. Mark, thanks for the question. You know, with regards to the process from an actual review perspective, as we've stated previously, it was very straightforward. Now when we filed our NDA, you know, unfortunately, we filed it right at the beginning of a historic pandemic, which affected and disrupted companies as well as all kinds of government organizations. You know, we're grateful and understanding of the FDA needing the time that it needed in order to take action on our application. With regards to the PMCs and the PMRs, they're pretty standard ones. You know, for example, one of them is to do a maintenance study, which is a standard requirement for antidepressant drugs, which are approved initially. We're gonna do that. We did mention that some of the PMRs do include some follow on non-clinical studies, which clearly were not required at the time of approval. We'll be doing those. Nothing out of the ordinary. Was there ever a discussion about actually getting a label that said, you know, approved for with fast onset? Or was that always the plan that it was gonna be in the label? As you can see for yourself, you know, the label does have that onset of action was pre-specified. That's something that we did look for. And it made it into the label. I think it speaks for itself. Then you talked about access. I was just curious, Lori, what have we heard so far as far as access? Does it sound like there'll be any issues or is this gonna be pretty standard? Yeah. You know, over, I think we started payer, you know, permitted payer discussions back, I think, back in April of 2021. You know, they, the Payer access team has been having discussions for quite some time now. All discussions that they have, you know, around the clinical benefits and the profile of the product, you know, have been very positive, right? The payers do recognize there's a high unmet need in MDD. They also recognize, you know, there's a mental health crisis happening right now, and they do recognize the novel mechanism of action, for Auvelity. We're encouraged and really looking forward to, you know, to starting those discussions with payers, around formulary access. I mean, is it? I guess just. You were breaking up there a little bit, Mark, but I think you were asking what the standard is, and it obviously varies by plan, per product, and per access strategy for companies. You know, once we discuss and reveal what our price is, we can start thinking about what our path to access looks like. Okay. Thanks. Thank you. Our next question has come from the line of Joseph Thome with TD Cowen. Your line is now open. Hi there. Good morning. Congratulations on getting this through, and thank you for taking our questions. Maybe just to follow up a little bit on the last one. In terms of, I mean, we were almost, you know, love to see it, but we're a little bit of a year, shy of a year past the initial PDUFA date. Were you able to uncover what the initial deficiencies that triggered that July letter last year were? Was there something that the FDA wanted comfort on, that you were able to tease apart over the past year? And then I know you mentioned they're gonna have some prior authorization assistance programs. What proportion of patients do you think are gonna need prior authorization? Is it everyone or is this gonna be certain plans? Thank you. Yeah. I'll take the first question with regards to you know what deficiencies were there. We disclosed all the deficiencies. As we've said before, the only deficiency that we were made aware of was related to CMC. We addressed that around the beginning of the year. But otherwise you know the review has been pretty smooth. Yeah. Hi. Thanks. The question around prior authorization. It's a little bit hard to say right now, especially because, you know, we haven't started the formulary discussions yet with payers. We do know, as per normal branded products launching, that prior authorizations will likely be required. What that percentage looks like, you know, it's way too early to tell. Okay. Maybe just one more quick one, 'cause I know the ex-US deal for Sunosi is gonna close in the Q4. Maybe how are you thinking about ex-US launches? Are you gonna try and do AXS-05 outside of the US? Any updates out there would be helpful. Thank you. Yes. What we've said that the corporate stance has been with regards to ex-U.S. is that we would look to partner outside of the U.S. You know, that has not changed. I think one of the things that we can say is with Sunosi and with us having ex-U.S. rights to Sunosi, and by the way, it's doing pretty well ex-U.S., it does increase with regards to business development outside of the U.S. Perfect. Thank you very much, and congrats again. Thank you. Our next question has come from the line, Matt Kaplan with Ladenburg Thalmann. Your line is now open. Hi, congrats on the approval, long awaited. Lori, maybe a question for you. How should we think about the rollout of payer access over, you know, following a launch, I guess, over the next 12 months, and how that would work? Yeah, it's a great question. Payers. You know. Oh, go ahead. Sorry, Matt. No. No. Please. Yeah. You know, think about it in terms of normal branded launches. You know, it takes a little bit of time to receive and get access and have those discussions with payers, which is one of the reasons why, you know, we feel very strongly in our patient support services and making sure that patients and physicians can write the product and patients can have access. We, you know, like I mentioned, you know, we intend to start our discussions very soon. You know, it should move at a normal new branded launch pace. Okay. That's helpful. I guess, maybe just to follow up another question with respect to where do you think docs will initially utilize the drug, and will it be in newly diagnosed patients, or do you expect a lot of what's called switching of patients that don't adequately respond to their current therapies? Yeah. You know, I think Herriot Tabuteau said it really well, you know, earlier when he answered a similar type question, which is, you know, 2/3 of patients don't respond to therapy that's out there right now. There is a very high unmet need, and the clinical benefits that Auvelity brings, you know, to the table. We believe that physicians, you know, will be able to choose the right patients for the product easily because of the data that spans, you know, basically a very broad indication of MDD. Great. Well, congrats again, and thanks for taking the questions. Thank you. Our next question comes from the line of Yatin Suneja with Guggenheim. Your line is now open. Good morning, and congratulations on the approval. This is Eddie on for Yatin. Can you just talk a little bit about how you were thinking about providing guidance next year for the launch? Would you provide updates on scripts or revenue or payer negotiations? Are there any recent drug comps in the depression space that may help us model sort of how quickly this may ramp up next year? Thanks. Yeah, I'll take both of those, actually, and then maybe Nick can chime in on providing guidance. You know, the metrics that we will track will be, you know, normal launch metrics, and everything that you just said there, right? Patient adoption, HCP writing, you know, the access that opens up. You know, we will be tracking, you know, all the normal launch related metrics. In terms of providing guidance from a revenue standpoint, I'll let Nick comment on that. Yeah, I think it's obviously Eddie, thanks for the question. It's obviously really early right now to think about giving sales guidance and, you know, we'll be able to give you guys more insight as we launch and later this year. Thanks. Eddie, I Oh, go ahead, sorry. No, go ahead, please. Please. I was just gonna follow up and say, like, does getting this initial approval change your plans for the Alzheimer's agitation filing? Do you expect that to be an sNDA with only one study, or do you think you'll need both ACCORD and ADVANCE-2 in light of this initial approval? Thanks. It doesn't change our plans, our clinical development plans with regards to Alzheimer's disease agitation. A very important indication. You know, we will continue to develop the product and conduct the studies that we are conducting. Whether or not, you know, we file it as an NDA or as a regular NDA, that is a decision that we will make at the time of the pre-NDA meeting for that indication. Eddie, I didn't answer your first questions, your initial questions about analogs for recent MDD launches. There hasn't been a branded MDD with a label for broad-based MDD launch in over a decade. You know, that would be a slightly different analog to look at. Great. Thanks. Congratulations, guys. Thank you. Our next question comes from the line of Jason Gerberry with Bank of America. Your line is now open. Oh, hey, guys. Thank you for taking my question. I just wanted to, and first off, congrats on the approval. Clarify the 165 sales reps, are those all new reps or is that inclusive of some of the Sunosi sales reps that you have? As we think about sort of digital-centric spend, how does that compare to other mediums, right? I'm just kinda curious, like typically, you know, non-rep spend might be kind of at a one-to-one ratio with rep spend, but I imagine digital-centric dollars out might be not as expensive. Just, you know, any clarity you can provide just in sort of that step up in SG&A associated with the launch. Sorry, I have a cough. How do you see physicians using, you know, payers are slotting for treatment-resistant patients. How do you see that impact of the treatment-resistant depression study potentially impacting rollout of the drug? Thanks. Okay. I'll try to take those off. Sales reps. The first of all, I, you know, pretty adamant that our sales forces stay separated at launch. As I've mentioned on several Sunosi calls, you know, eventually we will, you know, recognize those synergies. Sunosi is starting to perform really well right now, and so that sales team is focused and really, you know, doing what they need to do. The Auvelity field force, you know, I would be remiss if I didn't say this out loud. The sales leaders that we hired over a year ago have been able to recruit and maintain 165 sales reps for over a year. You know, maintaining that high caliber engagements that you know really generates the excitement around the product and Axsome and the opportunity. You know, incredibly impressive effort from the sales leaders that you know again were hired over a year ago to recruit for 165 positions. Our hiring process was extremely competitive. We ended up accepting only 3% of the applicants that came in, and over 98% of the field force have CNS experience. Really excited about you know the field force that we have coming on board. You know, as I mentioned, your original question around are they separate? This will be a completely new sales force. Second question around DTC spend. Yes, we do anticipate that it will be, you know, slightly less than your traditional model, or not even slightly, significantly less than your traditional model. If you think about broad-based, broad-net spend around, you know, DTC TV, these are very, very expensive, you know, endeavors, where you're casting a wide net and trying to catch, you know, a certain amount to get an ROI. With DCC, the spend is much, you know, narrower because we are highly targeted at, you know, how we are approaching those targets, either patients or HCPs through digital means. Then the slotting of TRD, that one, that one's a bit hard for me. We, you know, it, the label is broad-based MDD. All physicians that we speak to are not slotting this product towards TRD. Got it. Great. Thanks. Thank you. We'll take one more set of questions, and our next questions are from the line of David Wong with SMBC. Your line is now open. Hey, everyone. Let me just echo the congrats and, you know, really great to see the product approved. I just had some a few questions on maybe some initiating the label. First, you know, with starting patients on the product, I just see that it, you know, it recommends docs kind of assess past medical history and if they're receiving other products that might have bupropion and dextromethorphan. You know, is the idea there that they would just, if that were the case, they would just have to be weaned off those products or stop those products? Secondly, with the, you know, the dosage, it looks like they titrate up, one tablet for three days and then going to, you know, two tablets on day three, I guess. Is that something that docs would be comfortable to have patients, you know, receive that instruction and I assume do that in the, you know, comfort of their home? Sure. Thank you for the questions. With regards to patients being on other meds, it is common that patients are on other medications whenever they're prescribed a new medication. If doctors are very familiar with taking patients, weaning patients off of meds, you know, typically what would happen would be that patients would be weaned off a medication that they're on for a certain number of half-lives to make sure that they're clear of that medication. This is something that psychiatrists are very familiar with and which is common. Then with regards to the titration. The titration is. It's a very simple titration, which is, you take 1 tablet once a day for three days and then twice daily thereafter. A very simple titration and one that patients obviously will be able to do at home and which is very clearly communicated, which can be very clearly communicated to patients. Again, pretty, you know, I wouldn't say, you know, standard for all drugs, but a very standard type of procedure and instruction set for patients which is easy to follow. Okay. Thanks so much. This does end our question and answer session. I would now like to pass the conference back to the management team for closing remarks. Well, well, thank you again for joining us on the call today. We are thrilled to be making Auvelity available to patients with MDD. We would like to especially thank the patients and the investigators who participated in the clinical trials of Auvelity. With the approval of Auvelity and the recent acquisition of Sunosi, Axsome will now be commercializing two important new CNS products. In addition, the rest of our pipeline continues to advance with phase III trials of AXS-12 in narcolepsy and AXS-05 in Alzheimer's disease agitation, as well as the anticipated NDA filing of AXS-14 in fibromyalgia next year. We are committed to bringing these potentially life-changing medicines to people living with serious CNS conditions. We look forward to updating you on our continued progress in the coming months. Have a great day. Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.